ProSAAS neuropeptides and receptors GPR171 and GPR83: Potential therapeutic applications for pain, anxiety, and body weight regulation.

Peptides derived from the precursor named proSAAS are some of the most abundant peptides present in the brain, with levels comparable to enkephalin, neuropeptide Y, and several other well-studied neuropeptides. Despite their abundance, the proSAAS-derived peptides are not well-known by the scientific community. In the ∼25 years since their discovery, much has been learned about the role of several of these peptides and their receptors, with functions including energy balance and body weight regulation, fear, anxiety, reward behavior, and pain. This review provides an overview of this emerging field and outlines important areas for further studies. SIGNIFICANCE STATEMENT: Neuropeptides perform important roles in cellular signaling and their receptors are the targets of hundreds of distinct pharmacotherapies. The peptides derived from proSAAS are highly abundant and broadly expressed in the brain, and their receptors represent an emerging target for novel therapeutics.